A Study to Assess the Safety and Efficacy of Omarigliptin (MK-3102) in Participants With Type 2 Diabetes Mellitus (T2DM) and Inadequate Glycemic Control (MK-3102-011)

This study has been completed.

Sponsor:

Merck Sharp & Dohme Corp.

ClinicalTrials.gov Identifier:

NCT01717313

First Posted: October 30, 2012

Last Update Posted: July 25, 2016

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
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The purpose of this study is to assess the safety and efficacy of omarigliptin (MK-3102), dosed once-weekly in participants with T2DM who have inadequate glycemic control on diet and exercise. The primary hypothesis is that after 24 weeks, treatment with omarigliptin compared with placebo provides greater reduction in hemoglobin A1c (A1C).

A1C (%) is used to report average blood glucose levels over prolonged periods of time.

Because it was discovered that in another omarigliptin study (MK-3102-028, NCT01814748) subjects had taken metformin (prohibited per protocol, and taken without investigator knowledge), after unblinding of Phase A of this study, an analysis of metformin levels was performed on stored Week 18 blood samples. Of the subjects not rescued with metformin prior to Week 18, 10% in the omarigliptin group and 20% in the placebo group had levels showing that they were taking metformin (prohibited per protocol). The use of prohibited metformin disproportionately by the placebo group may have resulted in a smaller than expected treatment effect for efficacy outcome measures (see post-hoc analysis).

Percentage of Participants Who Experienced at Least One Adverse Event in Phase A (Excluding Data After Glycemic Rescue, Safety Population) [ Time Frame: Up to 27 weeks ]

An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions.

This analysis may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).

Percentage of Participants Who Discontinued From the Study Drug Due to an Adverse Event in Phase A (Excluding Data After Glycemic Rescue, Safety Population) [ Time Frame: Up to 24 weeks ]

An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions.

This analysis may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).

Percentage of Participants Who Experienced at Least One Adverse Event (Phase A + Phase B, Excluding Data After Glycemic Rescue, Safety Population) [ Time Frame: Up to 57 weeks ]

An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions.

This analysis may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).

Percentage of Participants Who Discontinued From the Study Drug Due to an Adverse Event (Phase A + Phase B, Excluding Data After Glycemic Rescue, Safety Population) [ Time Frame: Up to 57 weeks ]

An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions.

This analysis may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).

A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). The percentage of participants who achieved A1C values <7.0% (53 mmol/mol) in the FAS population at Week 24.

Because it was discovered that in another omarigliptin study (MK-3102-028, NCT01814748) subjects had taken metformin (prohibited per protocol, and taken without investigator knowledge), after unblinding of Phase A of this study, an analysis of metformin levels was performed on stored Week 18 blood samples. Of the subjects not rescued with metformin prior to Week 18, 10% in the omarigliptin group and 20% in the placebo group had levels showing that they were taking metformin (prohibited per protocol). The use of prohibited metformin disproportionately by the placebo group may have resulted in a smaller than expected treatment effect for efficacy outcome measures (see post-hoc analysis).

A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). The percentage of participants who achieved A1C values <6.5% (48 mmol/mol) in the FAS population at Week 24.

Because it was discovered that in another omarigliptin study (MK-3102-028, NCT01814748) subjects had taken metformin (prohibited per protocol, and taken without investigator knowledge), after unblinding of Phase A of this study, an analysis of metformin levels was performed on stored Week 18 blood samples. Of the subjects not rescued with metformin prior to Week 18, 10% in the omarigliptin group and 20% in the placebo group had levels showing that they were taking metformin (prohibited per protocol). The use of prohibited metformin disproportionately by the placebo group may have resulted in a smaller than expected treatment effect for efficacy outcome measures (see post-hoc analysis).

Blood glucose was measured on a fasting basis (collected after an 10-hour fast). FPG is expressed as mg/dL. This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0.

Because it was discovered that in another omarigliptin study (MK-3102-028, NCT01814748) subjects had taken metformin (prohibited per protocol, and taken without investigator knowledge), after unblinding of Phase A of this study, an analysis of metformin levels was performed on stored Week 18 blood samples. Of the subjects not rescued with metformin prior to Week 18, 10% in the omarigliptin group and 20% in the placebo group had levels showing that they were taking metformin (prohibited per protocol). The use of prohibited metformin disproportionately by the placebo group may have resulted in a smaller than expected treatment effect for efficacy outcome measures (see post-hoc analysis).

Because it was discovered that in another omarigliptin study (MK-3102-028, NCT01814748) subjects had taken metformin (prohibited per protocol, and taken without investigator knowledge), after unblinding of Phase A of this study, an analysis of metformin levels was performed on stored Week 18 blood samples. Of the subjects not rescued with metformin prior to Week 18, 10% in the omarigliptin group and 20% in the placebo group had levels showing that they were taking metformin (prohibited per protocol). The use of prohibited metformin disproportionately by the placebo group may have resulted in a smaller than expected treatment effect for efficacy outcome measures (see post-hoc analysis).

A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Thus, this change from baseline reflects the Week 54 A1C minus the Week 0 A1C.

The results of the study at Week 54 may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).

A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). The percentage of participants who achieved A1C values <6.5% (48 mmol/mol) in the FAS population at Week 54.

The results of the study at Week 54 may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).

If necessary, participants may have glycemic rescue therapy initiated with open-label metformin during Phase A of the study. Participants in the placebo treatment group who were not rescued with open-label metformin during Phase A will receive blinded metformin (starting at 500 mg orally twice daily with up-titration to 1000 mg orally twice daily) in Phase B. Participants in the omarigliptin treatment group who were rescued with open-label metformin in Phase A will continue open-label metformin during Phase B of the study.

Other Names:

Fortamet®

Glucophage®

Glucophage® XR

Glumetza®

Riomet®

Metgluco®

Glycoran®

Drug: Placebo to metformin

During Phase B of the study, participants in the omarigliptin treatment group who did not initiate glycemic rescue therapy during Phase A will receive placebo to metformin for 30 weeks (Phase B of the study).

Drug: Glimepiride

If necessary during Phase B of the study, participants will initiate open-label glimepiride as glycemic rescue therapy

Other Name: Armaryl®

Placebo Comparator: Placebo to Omarigliptin

Placebo to omarigliptin administered orally once a week for 24 weeks (Phase A) followed by placebo to omarigliptin administered orally once a week plus metformin daily for an additional 30 weeks (Phase B). Open-label metformin was to be initiated for participants meeting protocol-specified glycemic criteria during Phase A, but was otherwise prohibited. Open-label glimepiride daily may be initiated as glycemic rescue therapy during Phase B.

Drug: Placebo to Omarigliptin

Placebo to omarigliptin capsule administered orally once a week

Drug: Metformin

If necessary, participants may have glycemic rescue therapy initiated with open-label metformin during Phase A of the study. Participants in the placebo treatment group who were not rescued with open-label metformin during Phase A will receive blinded metformin (starting at 500 mg orally twice daily with up-titration to 1000 mg orally twice daily) in Phase B. Participants in the omarigliptin treatment group who were rescued with open-label metformin in Phase A will continue open-label metformin during Phase B of the study.

Other Names:

Fortamet®

Glucophage®

Glucophage® XR

Glumetza®

Riomet®

Metgluco®

Glycoran®

Drug: Glimepiride

If necessary during Phase B of the study, participants will initiate open-label glimepiride as glycemic rescue therapy

Other Name: Armaryl®

Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Has type 2 diabetes mellitus

Participants in India must be ≤65 years of age

Meets one of the following criteria: currently not on an antihyperglycemic agent (AHA) for >= 12 weeks and has an A1C of >=7% and <=10% or on stable AHA monotherapy or low-dose combination therapy for > 12 weeks and has an A1C of >=6.5% and <=9%

Participant is one of the following: male, female who is not of reproductive potential, female of reproductive potential who agrees to remain abstinent from heterosexual activity or use (or have their partner use) acceptable contraception to prevent pregnancy during the study and for 21 days after the last dose of study drug

Exclusion Criteria:

History of type 1 diabetes mellitus or a history of ketoacidosis

Has been treated with: a thiazolidinedione (TZD) within 4 months of study participation, a glucagon-like peptide-1 (GLP-1) receptor mimetic or agonist or dipeptidyl peptidase IV (DPP-4) inhibitor within 6 months of study participation, insulin or sodium-glucose cotransporter inhibitor within 12 weeks of study participation, omarigliptin at any time prior to study participation

History of hypersensitivity to DPP-4 inhibitor

History of intolerance, hypersensitivity or any contraindication to metformin and/or glimepiride or other sulfonylurea

Is on a weight loss program and not in the maintenance phase or has started a weight loss medication in the past 6 months or has undergone bariatric surgery within 12 months prior to study participation

Has undergone a surgical procedure within 4 weeks of study participation or has planned major surgery during the study

Is on or likely to require treatment for ≥14 consecutive days or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted)

Is currently being treated for hyperthyroidism or is on thyroid hormone therapy and has not been on a stable dose for at least 6 weeks

Is expecting to undergo hormonal therapy in preparation to donate eggs during the study, including 21 days following the last dose of study drug

Has had new or worsening coronary heart disease or congestive heart failure within the past 3 months, or has any of the following disorders within the past 3 months: acute coronary syndrome, coronary artery intervention, stroke or transient ischemic neurological disorder

Has poorly controlled hypertension

History of malignancy <=5 years prior to study participation, except for basal cell or squamous cell skin cancer or in situ cervical cancer

Pregnant or breastfeeding, or is expecting to conceive during the study, including 21 days following the last dose of study drug

User of recreational or illicit drugs or has had a recent history of drug abuse

Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking

Has donated blood products or has had a phlebotomy within 8 weeks of study participation, or intends to donate blood products during the study or has received, or is anticipated to receive, blood products within 12 weeks of study participation or during the study

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01717313